Germinated brown rice protects against glutamate toxicity in HT22 hippocampal neurons through the jnk-mediated apoptotic pathway via the GABAA receptor.

The anti-apoptosis effect of germinated brown rice (GBR) focusing on differentiated HT22 cells results in improved nutritional values after the germination process of GBR which contains total phenolic compounds and γ-aminobutyric acid (GABA). Cell death induced by 5 mM glutamate was investigated for 24 h to determine whether GBR mediates cell death through GABA receptors by using antagonists. The results showed that GBR (100 µg/ml) suppressed glutamate-induced cytotoxicity and caused arrest at the G1/S phase of the cell cycle in differentiated HT22 cells. Furthermore, GBR significantly decreased the expression level of c-Jun, while its active form, p-c-Jun, is the downstream product of the JNK-mediated apoptotic pathway and causes subsequent cell death. In addition, bicuculline (12.5 nM), a GABAA antagonist, could eliminate GBR effects, but phaclofen (1 mM), a GABAB antagonist, could not. Surprisingly, GBR exhibited a better neuroprotective effect than a pure commercial GABA compound (0.115 µM). These results indicated that GBR possessed high anti-apoptotic activity and inhibited cell death in differentiated HT22 cells by perturbing re-entry of the cell cycle and apoptosis via the GABAA receptor. Hence, GBR could be further used as a valuable nutritional compound to prevent apoptosis-induced neurodegenerative diseases.

Standardized Extract of Centella asiatica Prevents Fear Memory Deficit in 3xTg-AD Mice.

ECa 233 is a standardized extract of Centella asiatica (CA), an herb widely used in traditional Chinese and Ayurvedic medicine. Previous studies reported that ECa 233 enhanced memory retention and synaptic plasticity in the hippocampus of healthy rats. Because of this, we became curious whether ECa 233 has a therapeutic effect on the fear memory deficit in the triple transgenic Alzheimer's disease (3xTg-AD) model mice. Fear memory is a crucial emotional memory for survival that is found to be impaired in patients with early-onset Alzheimer's disease (AD). In this study, we orally administered ECa 233 (doses: 10, 30, and 100[Formula: see text]mg/kg) to 3xTg-AD mice, who were five months old, for 30 consecutive days. We found that ECa 233 prevented a cued fear memory deficit and enhanced hippocampal long-term potentiation (LTP) in 3xTg-AD mice. Subsequent proteomic and western blot analyses revealed increased expression levels of the molecules related to LTP induction and maintenance, including brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB) and its network proteins, and extracellular signal-regulated kinase 1 and 2 (ERK1 and 2) in the hippocampi and amygdala of 3xTg-AD mice after ECa 233 pre-treatment. Our results indicate that ECa 233 is a promising potential herbal standardized extract that could be used in preventing the fear memory deficit and synaptic dysfunction before the early onset of AD.

Age and gender differences for the behavioral phenotypes of 3xTg alzheimer's disease mice.

The triple transgenic Alzheimer's disease (3xTg-AD) strain is a common mouse model used for studying the pathology and mechanism of Alzheimer's disease (AD). The 3xTg-AD strain exhibits two hallmarks of AD, amyloid beta (Aß) and neurofibrillary tangles. Several studies using different gender and age of 3xTg-AD mice to investigate their behavior phenotypes under the influence of various treatments have reported mixed results. Therefore, a comprehensive investigation on the optimal gender, age, and training paradigms used for behavioral studies of 3xTg-AD is necessary. In the present study, we investigated the behavioral phenotypes for the two genders of 3xTg-AD mice at 3, 6, 9, and 12 months old and compared the results with age-, gender-matched C57BL/6N control strain. All mice were subjected to tail flick, pinprick, open field, elevated plus maze, passive avoidance, and trace fear conditioning (TFC) tests to evaluate their sensory, locomotor, anxiety, and learning/memory functions. The results showed that TFC on male 3xTg-AD mice is optimal for studying the memory performance in AD. The sensory and locomotor functions of 3xTg-AD mice for two genders appear to be normal before 6 months, decline in fear memory afterwards. The differences between control and 3xTg-AD male mice in contextual and cued memory are robust, thus they are ideal for evaluating the effect of a treatment. Since it is costly and time consuming to obtain wildtype littermates as controls, C57BL/6N strain is suggested to be used as control mice because their baseline performance of sensorimotor functions are similar to that of 3xTg-AD mice.

The 4-(Phenylsulfanyl) butan-2-one Improves Impaired Fear Memory Retrieval and Reduces Excessive Inflammatory Response in Triple Transgenic Alzheimer's Disease Mice.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by an excessive inflammatory response and impaired memory retrieval, including spatial memory, recognition memory, and emotional memory. Acquisition and retrieval of fear memory help one avoid dangers and natural threats. Thus, it is crucial for survival. AD patients with impaired retrieval of fear memory are vulnerable to dangerous conditions. Excessive expression of inflammatory markers is known to impede synaptic transmission and reduce the efficiency of memory retrieval. In wild-type mice, reducing inflammation response can improve fear memory retrieval; however, this effect of this approach is not yet investigated in 3xTg-AD model mice. To date, no satisfactory drug or treatment can attenuate the symptoms of AD despite numerous efforts. In the past few years, the direction of therapeutic drug development for AD has been shifted to natural compounds with anti-inflammatory effect. In the present study, we demonstrate that the compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) is effective in enhancing fear memory retrieval of wild-type and 3xTg-AD mice by reducing the expression of TNF-α, COX-2, and iNOS. We also found that 4-PSB-2 helps increase dendritic spine density, postsynaptic density protein-95 (PSD-95) expression, and long-term potentiation (LTP) in the hippocampus of 3xTg-AD mice. Our study indicates that 4-PSB-2 may be developed as a promising therapeutic compound for treating fear memory impairment of AD patients.

Enhanced contextual fear memory in peroxiredoxin 6 knockout mice is associated with hyperactivation of MAPK signaling pathway.

Fear dysregulation is one of the symptoms found in post-traumatic stress disorder (PTSD) patients. The functional abnormality of the hippocampus is known to be implicated in the development of such pathology. Peroxiredoxin 6 (PRDX6) belongs to the peroxiredoxin family. This antioxidant enzyme is expressed throughout the brain, including the hippocampus. Recent evidence reveals that PRDX6 plays an important role in redox regulation and the modulation of several signaling molecules involved in fear regulation. Thus, we hypothesized that PRDX6 plays a role in the regulation of fear memory. We subjected a systemic Prdx6 knockout (Prdx6-/-) mice to trace fear conditioning and observed enhanced fear response after training. Intraventricular injection of lentivirus-carried mouse Prdx6 into the 3rd ventricle reduced the enhanced fear response in these knockout mice. Proteomic analysis followed by validation of western blot analysis revealed that several proteins in the MAPK pathway, such as NTRK2, AKT, and phospho-ERK1/2, cPLA2 were significantly upregulated in the hippocampus of Prdx6-/- mice during the retrieval stage of contextual fear memory. The distribution of PRDX6 found in the astrocytes was also observed throughout the hippocampus. This study identifies PRDX6 as a participant in the regulation of fear response. It suggests that PRDX6 and related molecules may have important implications for understanding fear-dysregulation associated disorders like PTSD.

4-(Phenylsulfanyl) Butan-2-One Attenuates the Inflammatory Response Induced by Amyloid-ß Oligomers in Retinal Pigment Epithelium Cells.

Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aß) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer's disease (AD) patients. Extracellular deposition of Aß can induce the expression of inflammatory cytokines such as IL-1ß, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aß1-42 oligomer (oAß1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAß1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.

Germinated Brown Rice Attenuates Cell Death in Vascular Cognitive Impaired Mice and Glutamate-Induced Toxicity In HT22 Cells.

Germinated brown rice (GBR) with unpolishing, soaking, and germinating processes can improve the texture, flavor, and nutritional value, including GABA and phenolic contents. The effect of GBR was first investigated in vascular cognitive impaired mice and glutamate-induced toxicity in HT22 cells with respect to standard pure GABA. Feeding mice with GBR for 5 weeks showed neuroprotection. In this study, the modified bilateral common carotid artery occlusion mice model was mild but a significant difference in cognitive impairment was still shown. Like pure GABA, GBR decreased cognitive deficits in memory behavioral tests and significantly attenuated hippocampal neuronal cell death at P < 0.001. Similarly to 0.125 µM of GABA, 100 µg/mL of GBR increased HT22 cell viability after glutamate toxicity. GBR affected less apoptotic cell death and less blocking by the GABAA antangonist bicuculline in comparison to GABA. When the results are taken together, the underlying mechanism of GBR protection may mediate though the GABAA receptor and its phenolic contents.

Effect of Centella asiatica on pathophysiology of mild chronic cerebral hypoperfusion in rats.

OBJECTIVE: The present study investigated the effect of standardized Centella asiatica extract on cognition and hippocampal pathology of mild chronic cerebral hypoperfusion (CCH) that was induced by permanent right common carotid artery occlusion (RCO) in rats. MATERIALS AND METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into four groups of Sham-veh, Sham-C. asiatica, RCO-veh and RCO-C. asiatica, which were further divided into short-term and long-term CCH induction. Oral treatments with 20 mg/kg C. asiatica initiated 24 hours and 12 months after CCH and continued for 14 consecutive days. According to the cognition and histopathological evaluation period, the experiment was divided into 2 sets of either 2 or 12 months of CCH. RESULTS: Results showed that 2-month CCH induced learning flexibility deficit associated with CA1 neuronal damage and internal capsule (IC) astroglia activation. Long-lasting (12 months) mild CCH induced spatial learning, memory and flexibility deficits associated with progressive dorsal hippocampal damage. Treatment with 20 mg/kg of C. asiatica improved learning flexibility deficit after 2 and 12 months of CCH. C. asiatica ameliorated neuronal damage in the dorsal hippocampus at 2 months of CCH when given 24 hours after CCH onset. Treatment with C. asiatica after 12 months of cerebral blood flow reduction improved memory and learning flexibility deficits and was associated with the dentate gyrus neuronal damage reduction. CONCLUSION: Our finding indicates the therapeutic potential of C. asiatica either when given immediately after ischemic insult or when administered one year after ischemic insult, in a CCH rat model.

Anatomy of medial plantar superficial branch artery perforators: Facilitation of medial plantar superficial branch artery perforator (MPAP) flap harvesting and design for finger pulp reconstruction.

BACKGROUND: Medial plantar artery perforator (MPAP) flap was proposed as proper option for finger pulp reconstruction. To provide the previously unavailable vessel information required for this small flap design, this study aimed to gather all necessary anatomy of MPA, MPAP, and their territories of blood supply to apply in clinical MPAP flap reconstruction minimizing perforator injury. METHODS: Dissection of 30 Thai cadaveric feet for visualizing superficial branch of MPA and its perforators (MPAP) using acrylic dye cannulation were performed. Diameter, length, number of branches, course, distributing areas of these vessels, and also their areas of blood supply were recorded in relation to specified landmarks, eg, C-MTH line; medial calcaneal tuberosity to plantar side of the first metatarsal head and S point; emerging point of superficial branch of MPA from deep fasciae into subcutaneous layer. RESULTS: Average diameter of MPA at its origin and total length are 1.63 ± 0.3 and 52.8 ± 16.1 mm, respectively. It provides 1-3 perforators, with an average size and length of 0.36 ± 0.11 and 23.2 ± 5.47 mm, respectively. Its distribution is mostly in the posteromedial quadrant within 50 and 30 mm from the midpoint of C-MTH line and the S point, respectively. The estimated perforator flap area is 2.5 cm × 1.5 cm and 4.5 cm × 2.5 cm for single and double perforators, respectively. CONCLUSIONS: MPAP flap was proved as another ideal option for finger pulp reconstruction. Its limitation is small size of perforators but this can be overcome by using MPA for microsurgical anastomosis instead.

Vascular Nature and Existence of Anastomoses of Extrinsic Postauricular Fascia: Application for Staged Auricular Reconstruction.

A staged auricular reconstruction in microtia patients was developed by using superficial mastoid fascia (as part of extrinsic postauricular fascia) to cover the cartilagenous framework due to its highly vascularized nature. Three branches of external carotid artery (superficial temporal artery, posterior auricular artery and occipital artery) were found to supply this fascia, this study was therefore aimed to investigate the dimension of blood supply from each vessel and also to demonstrate the existence of anastomoses among these arteries. Thirty-eight pinnas and postauricular fascias from Thai fresh adult cadavers were included to document the anastomoses by showing both perfused dye connection (10 dissections) and visible anastomotic branches (8 dissections) among them. Distribution of each vessel trunk and its branches were demonstrated using superimposed illustration in the other 20 dissections with dye injection into each artery to designate 3 zones of anastomotic area between each arterial pair. Maximal size of viable postauricular fascial flap for staged reconstruction according to this vascular study was thus estimated to be at least 5 cm above and 3 cm below the Frankfurt horizontal plane and about 6 cm posterior to external acoustic meatus owing to the course of posterior auricular artery and its anastomoses. In addition, greater size of flap with dual blood supply from both superficial temporal and posterior auricular arteries can be raised by harvesting beyond 5 cm above external acoustic meatus.

Neuroprotective Effects of Germinated Brown Rice in Rotenone-Induced Parkinson's-Like Disease Rats.

The effects of germinated brown rice (GBR) on the motor deficits and the dopaminergic (DA) cell death were investigated in Parkinson's-like disease (PD) rats. Reactive oxidative species generated by chronic subcutaneous injection of rotenone (RT) lead to neuronal apoptosis particularly in the nigrostriatal DA system and produce many features of PD, bradykinesis, postural instability and rigidity. In this study, 4-phenylbutyric acid (4-PBA), previously reported to inhibit RT-induced DA cell death, was used as the positive control. Results show that pretreatment with GBR as well as 4-PBA significantly enhanced the motor activity after RT injection, and GBR affected significantly in open field test, only in the ambulation but not the mobility duration, and ameliorated the time to orient down (t-turn) and total time to descend the pole (t-total) in pole test as compared to RT group, but significantly lowered both t-turn and t-total only in 4-PBA group. The percentage of apoptotic cells in brain measured by flow cytometry and the inflammatory effect measured by ELISA of TNF-α showed significant increase in RT group as compared to the control (CT) group at P < 0.05. Apoptotic cells in RT group (85.98 %) showed a significant (P < 0.05) increase versus CT group (17.50 %), and this effect was attenuated in GBR+RT group by decreasing apoptotic cells (79.32 %), whereas, increased viable cells (17.94 %) versus RT group (10.79 %). GBR in GBR + RT group could decrease TNF-α both in the serum and in brain. In summary, GBR showed a neuroprotective effect in RT-induced PD rats, and it may be useful as a value-added functional food to prevent neurodegenerative disease or PD.

Alternative Landmarks of the Mandibular Foramen to Prevent Nerve Injury during Ramus Surgery.

OBJECTIVE: To investigate the mandibular foramen (MF) position in relation to other bony landmarks on the mandibular ramus (MR) to better understand the anatomical landmark during the ramus surgery. MATERIAL AND METHOD: Ninety-two adult mandibles were studied by measuring four linear parameters: AB, the distance from the posterior limit of the MF (point A) to the posterior border of the MR (point B), BC, the MR width (Point C was located at the anterior border of the MR), DE, the distance from the lingula tip (the highest and the most anterior limit of the MF) (point D) to the mandibular notch (point E), and the MR height (EF, point F was located at the mandibular inferior border). Lines BC and EF were drawn through points A and D and parallel to the inferior and posterior borders of the mandible, respectively. These measurements were analyzed to determine the mean parameters related to the MF location. RESULTS: The mean lengths of AB, BC, DE, and EF were 12.7 ± 2.3, 35.0 ± 4.0, 17.5 ± 3.5, and 52.7 ± 5.2 mm, respectively. The ratios between AB/BC and DE/EF were 0.36 ± 0.05 and 0.33 ± 0.05, respectively. This study indicated that the MF located slightly anterior to the posterior third of the MR width and at the superior third of the MR height. CONCLUSION: Anatomical consideration of this area is useful to prevent neurovascular injury when performing the bony cut made in a ramus osteotomy; however, pre-operative examinations with appropriate radiographic analysis are also recommended.

Reversible short-term and delayed long-term cognitive impairment induced by chronic mild cerebral hypoperfusion in rats.

Chronic cerebral hypoperfusion induced by aging in combination with vascular disorder potentially contributes to the development of vascular dementia. This study aimed to investigate the age-related changes in spatial performances in chronic mild cerebral hypoperfusion induced by permanent right common carotid artery occlusion (rCCAO) in rats. Four-month-old male Sprague-Dawley rats (n = 20) were randomly assigned into sham and rCCAO groups. Spatial performances of young adult rats (age 4-8 months) were evaluated repeatedly by the radial arm water maze at 6 days, and 1, 2 and 4 months after surgery. The spatial performance was re-assessed by the Morris water maze when the rats were 18 months old. The present results revealed that the rCCAO rats developed progressive deficit in spatial learning and memory, starting from day 6 and significant deficit was found at 2 months after rCCAO (p < 0.05). However, the spatial performance of the rCCAO rats was recovered at 4 months after surgery. Testing of the cognitive flexibility of the aged rCCAO rats (18 months old), indicated that the learning flexibility of the aged rCCAO rats was significantly impaired. This deficit was found in parallel with pronounced white matter damage in the corpus callosum and internal capsule and significant cell death in the dorsal hippocampus. Our results suggested that vascular risk insult in young adult rats resulted in spatial learning deficit which could be completely compensated later on. However, such previous vascular risk could be exacerbated by advancing age and subsequently lead to a deficit in cognitive flexibility with white matter damage and significant neuronal death in the dorsal hippocampus.

Postinjury administration of 17ß-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats.

The majority of spinal cord injuries (SCIs) in the clinic occur at the lower cervical levels, resulting in both white and gray matter disruption. In contrast, most experimental models of SCI in rodents induce damage in the thoracic cord, resulting primarily in white matter disruption. To address this disparity, experimental cervical SCI models have been developed. Thus, we used a recently characterized model of cervical hemicontusion SCI in adult male rats to assess the potential therapeutic effect of post-SCI administration of 17ß-estradiol. Rats received a hemicontusion at the level of the fifth cervical vertebra (C5) followed by administration of 17ß-estradiol via a slow release pellet (0.5 or 5.0 mg/pellet) beginning at 30 minutes post-SCI. Behavioral evaluation of skilled and unskilled forelimb function and locomotor function were conducted for 7 weeks after SCI. Upon conclusion of the behavioral assessments, spinal cords were collected and histochemistry and stereology were conducted to evaluate the effect of treatment on the lesion characteristics. We found that post-SCI administration of 17ß-estradiol decreased neuronal loss in the ventral horn, decreased reactive astrogliosis, decreased the immune response, and increased white mater sparing at the lesion epicenter. Additionally, post-SCI administration of 17ß-estradiol improved skilled forelimb function and locomotor function. Taken together, these data suggest that post-SCI administration of 17ß-estradiol protected both the gray and white matter in cervical SCI. Moreover, this treatment improved function on skilled motor tasks that involve both gray and white matter components, suggesting that this is likely a highly clinically relevant protective strategy.

Anatomical considerations of the Thai fibula used as a fibula osteocutaneous free flap in mandibular reconstruction and dental implant placement.

OBJECTIVE: Although the fibula osteocutaneous free flap has many proven advantages in restoring mandibular defects, the dimension of available fibula is one of its limitations. The present study aimed to investigate the suitability of dimensions and the quality of harvested fibulae for mandibular reconstruction and dental implant placement in Thais. MATERIAL AND METHOD: One hundred fourteen fibulae of 57 adult Thai cadavers were dissected. Total fibular length and the length of harvested fibula were measured. Dimensions of the fibula cross sections available for dental implant placement were recorded. Additionally, the cortical bone thickness and densities of cortical and spongy bones of 60 fibulae were assayed using cone beam computed tomography scan images. RESULTS: Mean total fibular length and mean length of harvested fibulae were 34.2 +/- 2.3 cm and 18.2 +/- 2.3 cm, respectively. A dental implant length of 7 to 10 mm could be placed in the fibula. The mean cortical bone thickness was 2.2 +/- 0.6 mm. The mean densities of the cortical and spongy bones were 614.4 +/- 148.8 HU and -600.6 +/- 228.7 HU, respectively. CONCLUSION: The present study suggests that, in Thais, a harvested fibula of 16 to 20 cm in length is sufficient to provide bone for reconstructing defected mandible and the dental implant placement is 7 to 10 mm in length. The mean cortical and spongy bone densities of fibula are less than that of the mandible in previous reports. The result supports the clinical experience using the fibula as donor site for the mandibular reconstruction and dental implant placement.

Occurrence of the foramen of Vesalius and its morphometry relevant to clinical consideration.

All 377 dry skulls were examined for the occurrence and morphometry of the foramen of Vesalius (FV) both in the middle cranial fossa and at the extracranial view of the skull base. There were 25.9% and 10.9% of FV found at the extracranial view of the skull base and in the middle cranial fossa, respectively. Total patent FV were 16.1% (11.9% unilaterally and 4.2% bilaterally). Most FV were found in male and on the left side. Comparatively, FV at the extracranial view of the skull base had a larger maximum diameter. The distance between FV and the foramen ovale (FO) was as short as 2.05 ± 1.09 mm measured at the extracranial view of the skull base. In conclusion, although the existence of FV is inconstant, its occurrence could not be negligible. The proximity of FV to FO should remind neurosurgeons to be cautious when performing the surgical approach through FO.

Anatomical consideration of pterion and its related references in Thai dry skulls for pterional surgical approach.

OBJECTIVE: Pterion is a crucial surgical landmark for surgical approaches to the middle meningeal artery particular lesions, and tumors in the brain. The present study aimed to analyze the types of the pterion and its location related with nearby landmarks in dry skulls. In addition, variations of pterion in sex, age, and skull side were compared. MATERIAL AND METHOD: Bilateral sides of 268 adult human Thai dry skulls were investigated Pterion types were classified as sphenoparietal, frontotemporal, epipteric, or stellate. To localize the pterion, linear distances were measured from the center of the pterion to neighboring landmarks. RESULTS: The results showed the two most common types of the pterion, the sphenoparietal (81.2%), and the epiteric (17.4%). Externally, the pterion was commonly located 38.48 +/- 4.38 mm superior to the zygomatic arch and 31.12 +/- 4.89 mm posterior to the frontozygomatic suture. Internally, it was located 38.94 +/- 3.76 mm lateral to the optic canal and 11.70 +/- 4.83 mm from the sphenoid ridge. Sex influenced the occurrence of thepterion type, while sex, skull side, and age affected its location. Mean skull thickness at the pterion was 5.13 +/- 1.67 mm. CONCLUSION: The pterion is predominantly sphenoparietal type and is typically located 39 mm superior to the zygomatic arch, 31 mm posterior to the frontozygomatic suture, 39 mm lateral to the optic canal and 12 mm from the sphenoid ridge. The data obtainedfrom the present study should be clinically useful for localizing the position of pterion.

The study of position of antilingula, midwaist of mandibular ramus and midpoint between coronoid process and gonion in relation to lingula of 92 Thai dried mandibles as potential surgical landmarks for vertical ramus osteotomy.

This study aims to investigate positions of the antilingula (AL), the midwaist of the mandibular ramus (MW) and the midpoint between the coronoid process and the gonion (MCG) in relation to the lingula of dried mandibles. Bilateral rami of 92 Thai dried mandibles were studied. The AL, the MW, the MCG and the corresponding position of the tip of lingula (L) were marked on the external aspect of the mandibular ramus. The distances from the AL, the MW and the MCG to the L were measured in the anterior-posterior and the superior-inferior planes using computerized image analysis. The results showed the AL was discernible in 80.4% of lateral mandibular rami studied. The most of the AL was found anterior-superior to the L with a maximum distance of 5.9 mm anteriorly and 8.2 mm superiorly. The MW was frequently located anterior-inferior to the L with a maximum distance of 9.3 mm anteriorly and 9.9 mm inferiorly. The majority of the MCG was found anterior-superior to the L with a maximum distance of 9.6 mm anteriorly and 8.9 mm superiorly. A 5 mm radius from the L included 84.5% of the AL, 81.5% of the MW and 79.4% of the MCG. Medians (interquartiles) of distances from the AL, the MW and the MCG to the L were 3.4 (2.3-5.0) mm, 3.8 (2.5-5.3) mm and 4.1 (2.8-5.3) mm, respectively. In conclusion, the AL was identified in 80.4% of lateral mandibular rami studied. The AL and the MCG were commonly found anterior-superior to the lingula, whereas the MW was mostly observed anterior-inferior to the lingula. Therefore, a cut made more than a 5 mm posterior or superior to these landmarks would be in 79% of cases, within a statistically safe area avoiding encroaching upon the inferior alveolar neurovascular bundle passing immediately lateral to the lingula. Although the MW and the MCG might be alternative surgical guides when the AL is absent, their use alone as surgical landmarks is not recommended.

Characterization of a graded cervical hemicontusion spinal cord injury model in adult male rats.

Most experimental models of spinal cord injury (SCI) in rodents induce damage in the thoracic cord and subsequently examine hindlimb function as an indicator of recovery. In these models, functional recovery is most attributable to white-matter preservation and is less influenced by grey-matter sparing. In contrast, most clinical cases of SCI occur at the lower cervical levels, a region in which both grey-matter and white-matter sparing contribute to functional motor recovery. Thus experimental cervical SCI models are beginning to be developed and used to assess protective and pharmacological interventions following SCI. The objective of this study was to characterize a model of graded cervical hemicontusion SCI with regard to several histological and behavioral outcome measures, including novel forelimb behavioral tasks. Using a commercially available rodent spinal cord impactor, adult male rats received hemicontusion SCI at vertebral level C5 at 100, 200, or 300 kdyn force, to produce mild, moderate, or severe injury severities. Tests of skilled and unskilled forelimb and locomotor function were employed to assess functional recovery, and spinal cord tissue was collected to assess lesion severity. Deficits in skilled and unskilled forelimb function and locomotion relating to injury severity were observed, as well as decreases in neuronal numbers, white-matter area, and white-matter gliosis. Significant correlations were observed between behavioral and histological data. Taken together, these data suggest that the forelimb functional and locomotor assessments employed here are sensitive enough to measure functional changes, and that this hemicontusion model can be used to evaluate potential protective and regenerative therapeutic strategies.